PROJECT SUMMARY A technology that can detect and quantify the kinetics of small molecule binding and biochemical reactions, such as post-translational protein modifications, is critical for understanding the mechanisms underlying cancer initiation and progression, for discovering cancer biomarkers, and for screening cancer drug candidates. Currently, the most widely used technology uses fluorescence labels, which is difficult for small molecules with sizes comparable to the fluorescent dyes, especially for quantitative kinetic information. Various label-free techniques have been developed, but their sensitivity diminishes with the molecular mass, making it extremely challenging to detect small molecules and biochemical reactions that involve small mass changes. To address this need, a charge sensitive optical detection (CSOD) technology will be developed in this project. CSOD is compatible with the standard microplate technology, making it attractive for high-throughput screening and analysis of molecular interactions and reactions. The basic principle was established with the support of an IMAT (Innovative Molecular Analysis Technologies for cancer research) R21 grant. In the present R33 project, the team will work closely with collaborators in academic research labs and pharmaceutical companies, and a bioanalytical instrument company to develop and validate the technology for the unmet need. The success of the project will lead to a new label-free high-throughput screening technology for measuring molecular interactions, particularly small molecule interactions and post-translational modifications. These processes are highly important for the research, diagnosis and treatment of cancer.